Abstract:
:The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding sites. However, the lower pA2 value for doxazosin at alpha 1-adrenoceptors in isolated thoracic aorta preparations suggests a lower potency compared to prazosin. The dose-related pressor effects of intravenous phenylephrine were used to assess vascular alpha 1-adrenoceptor antagonism in vivo. There was a close agreement between alpha 1-adrenoceptor antagonist potency and maximum hypotensive effects with both doxazosin and prazosin. The alpha 1-adrenoceptor antagonist effects of doxazosin were more prolonged than those of prazosin. Studies using either radioligand binding or pressor responses to B-HT 920 showed that doxazosin did not show any significant affinity for the alpha 2-adrenoceptor. Similarly, no direct vasodilator effects were observed either in animals administered angiotensin II or in isolated thoracic aorta spiral strip preparations contracted with potassium. Doxazosin has a longer terminal elimination half-life than prazosin. The pharmacokinetics of doxazosin were linear over the dose range examined. Following pharmacological 'autonomic blockade' and treatment with prazosin, doxazosin did not cause any further fall in blood pressure. These observations suggest that doxazosin, like prazosin, appears to exert its hypotensive action through alpha 1-adrenoceptor antagonism. The prolonged fall in blood pressure and well sustained alpha 1-adrenoceptor antagonism after doxazosin raise the possibility of an active metabolite which also has alpha 1-adrenoceptor blocking properties.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hamilton CA,Reid JL,Vincent Jdoi
10.1111/j.1476-5381.1985.tb09437.xsubject
Has Abstractpub_date
1985-09-01 00:00:00pages
79-87issue
1eissn
0007-1188issn
1476-5381journal_volume
86pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:It has been extensively reported that the leading anti-diabetic drug, metformin, exerts significant anticancer effects. This hydrophilic, cationic drug requires cation transporters for cellular entry where it activates its intracellular target, the AMPK signalling pathway. However, clinical resul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14694
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12225
更新日期:2013-07-01 00:00:00
abstract::1 The effects of alpha- and beta-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 beta-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10(-6)-10(-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09702.x
更新日期:1974-10-01 00:00:00
abstract::1. The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic rat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16193.x
更新日期:1994-09-01 00:00:00
abstract::ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the exte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08421.x
更新日期:1977-10-01 00:00:00
abstract::1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701083
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14164
更新日期:2018-05-01 00:00:00
abstract::1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702132
更新日期:1998-10-01 00:00:00
abstract::The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702517
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. EXPERIMENTAL APPROACH:The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02235.x
更新日期:2013-03-01 00:00:00
abstract::1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was without significant effect at doses of up to 200 nmol. 2. Intravenously administered BK indu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13962.x
更新日期:1993-12-01 00:00:00
abstract::Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physio...
journal_title:British journal of pharmacology
pub_type: 传,社论,历史文章
doi:10.1111/j.1476-5381.2009.00418.x
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The type-5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.71
更新日期:2008-05-01 00:00:00
abstract::1. N-formyl peptides (e.g. fMLP; N-formyl-L-methionyl-L-leucyl-phenylalanine) are potent mediators for inflammatory reactions. We report functional expression in Xenopus oocytes of human fMLP-R98 cDNA, without co-expression of the promiscuous G-protein subunit, Galpha-16. 2. Stimulation of voltage-clamped oocytes (-70...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704592
更新日期:2002-03-01 00:00:00
abstract::The effect of trimetazidine (TMZ), an anti-anginal drug, on the mechanical response of the guinea-pig ductus arteriosus placed under conditions of mild hypoxia (PO2 approximately equal to 75 mmHg) was investigated. When the PO2 of the bathing solution was 75 mmHg, TMZ caused a dose-dependent increase in tension. The m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb12936.x
更新日期:1985-02-01 00:00:00
abstract::1. Changes in membrane potential (measured with an intracellular microelectrode) and in cyclic nucleotide (adenosine 3':5'-cyclic monophosphate, cyclic AMP and guanosine 3':5'-cyclic monophosphate, cyclic GMP) levels (measured by radioimmunoassay) in response to inhibitory non-adrenergic non-cholinergic (NANC) field s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15804.x
更新日期:1990-06-01 00:00:00
abstract::Mouse spiders represent a potential cause of serious envenomation in humans. This study examined the activity of Missulena bradleyi venom in several in vitro preparations. Whilst female M. bradleyi venom at doses up to 0.05 microl ml(-1) failed to alter twitch or resting tension in all preparations used, male venom (0...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703494
更新日期:2000-08-01 00:00:00
abstract::1 The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats. 2 EDA inhibited, via a bicuculline-sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested. 3 The results with the analogues suggest that two amine groups...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08761.x
更新日期:1982-01-01 00:00:00
abstract::1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb17178.x
更新日期:1995-02-01 00:00:00
abstract::1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07372.x
更新日期:1975-03-01 00:00:00
abstract::For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threat...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2010.00964.x
更新日期:2010-11-01 00:00:00
abstract::An investigation of the effects of gamma-aminobutyric acid (GABA) and the selective GABAB receptor agonist, baclofen, on basal and stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in slices of rat cerebral cortex has been carried out. Neither GABA nor baclofen produced any significant change in basa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::1. Effects of morphine sulphate (1.25, 2.5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non-tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06866.x
更新日期:1972-10-01 00:00:00
abstract::1. Contractile responses to short trains of nerve stimulation have been characterized in small, medium and large arteries from the rat mesenteric circulation (5th - 6th, 2nd - 3rd and 1st order, respectively). In addition, sources of calcium for smooth muscle contraction have been investigated. 2. Nerve stimulation (1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703925
更新日期:2001-03-01 00:00:00
abstract::The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5-hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 microM) The potentiation was similar whether indomethacin was added 1 h before or during th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10714.x
更新日期:1983-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vasc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00825.x
更新日期:2010-09-01 00:00:00
abstract::1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2. Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 micrograms kg-1, i....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15260.x
更新日期:1996-03-01 00:00:00
abstract::The effects of 15-hydroperoxy metabolites of arachidonic acid on vascular tone were evaluated in the perfused mesenteric preparation, the isolated perfused lung and segments of pulmonary arteries of the rat. In the mesenteric preparation, precontracted with phenylephrine, both 15-hydroperoxy-5,8,11,13-eicosatetraenoic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11256.x
更新日期:1987-07-01 00:00:00
abstract::(1) Here, we introduce a beta-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[d-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. (2) This opioid-derived peptide possesses only low affinity for mu-receptors, but enhances the agonist binding to mu-receptors in v...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705416
更新日期:2003-09-01 00:00:00
abstract::1 Acetylcholine-induced contractions of the isolated chronically denervated soleus muscle of the mouse consist of two phases, but both phases are equivalent to the contracture phase seen in vivo.2 Low [Ca(2+)](0) (0.5-1.5 mM) augmented peak tension, as well as the rate of relaxation, of the first phase, but inhibited ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07556.x
更新日期:1977-12-01 00:00:00